Aims: The National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN) collected structured safety data in cocaine-dependent participants exposed to extended release naltrexone (XR-NTX) and buprenorphine/naloxone (BUP), or placebo (PLB).
Methods: A total of 302 cocaine-dependent individuals, aged 18-65, who met eligibility criteria, including either past-year opioid dependence or abuse, or past- year opioid use with a lifetime history of opioid dependence, were randomized to one of 3 treatment conditions: 16 mg BUP + XR-NTX (n=100), 4 mg BUP + XR-NTX (n=100), and PLB + XR-NTX (n=102). Induction complications, injection site reactions, liver function tests (LFTs), ECG, adverse events, serious adverse events and suicide risk were assessed.
Results: All participants were inducted onto XR-NTX, and 3 participants experienced withdrawal symptoms within the first 5 days of induction. A second XR-NTX dose was provided to 263 participants 4 weeks later. Eighty-eight participants experienced mild injection site reactions, of which 18 were moderate and none severe. Liver function tests remained within normal limits for the majority of participants; 10.3% and 7.0% had elevations of ALT and AST at baseline, and 8.7% and 7.3% at 4 weeks, respectively. ECG QTc prolongation was not observed. Of 37 SAEs reported only 2 were considered related to the intervention. Suicidal ideation was balanced across the arms of the trial.
Conclusions: This combination therapy of buprenorphine/naloxone and extended release naltrexone was well tolerated without evidence of significant safety issues surrounding induction, injection site reactions, perturbations of liver functions or ECG findings or unsolicited safety signals.